uniQure's Huntington's Gene Therapy Slows Disease at 4 Years, but the Benefit Narrows

uniQure announced additional data from its ongoing Phase I/II studies of AMT-130, its one-time gene therapy for Huntington's disease, on September 29. The therapy, now known by the generic name ifezuntirgene inilparvovec, uses a virus vector to deliver a microRNA designed to lower the huntingtin protein, and is administered in a single surgical procedure into a brain region called the striatum. In the four-year analysis, the 12 patients who received the high dose showed 44% slowing of disease progression on a commonly used rating scale compared with a matched external control group. That difference did not reach statistical significance.

The headline number is weaker than the one that carried the program this far. In September 2025, the same high-dose group showed 75% slowing at the three-year mark, which underpinned a U.S. Biologics License Application submitted earlier this month. On the functional capacity measure the company plans to use in its confirmatory study, uniQure says the absolute treatment benefit was maintained at 48 months, and a post-hoc analysis using the prior version of the external control showed 54% slowing on the rating scale and 68% on functional capacity.

uniQure's explanation for the narrowing gap centers on the control group, not the therapy: the updated external control dataset drawn from the ENROLL-HD natural history study contains, in the company's words, substantial missing data and survivor bias that likely underestimate how fast untreated patients decline. Executives called the four-year results unprecedented on an investor call. The market disagreed with the framing: the stock fell roughly 38% on Tuesday morning.

Announced is not the same as demonstrated. This was an open-label study of a small number of patients compared against a historical database rather than a randomized trial with a sham-surgery control, which is exactly what the FDA asked for earlier in 2026 before reversing course and accepting a submission based on the three-year data. The BLA now sits with the FDA for review, and uniQure plans a roughly 200-patient follow-up study that it aims to start before the end of the year.

Why it matters: Huntington's disease affects about 40,000 Americans, and existing drugs only ease symptoms. If AMT-130 holds up under regulatory scrutiny, it would be the first therapy that modifies the disease itself. The next year of FDA review and the design of the confirmatory study will decide whether that happens.